To get a comprehensive view of fungal M35 family (deuterolysin) and M36 family (fungalysin) genes, we conducted genome-wide investigations and phylogenetic analyses of genes in these two families from 50 sequenced Ascomycota fungi with different life styles. Large variations in the number of M35 family and M36 family genes were found among different fungal genomes, indicating that these two gene families have been highly dynamic through fungal evolution. Moreover, we found obvious expansions of Meps in two families of Onygenales: Onygenaceae and Arthodermataceae, whereas species in family Ajellomycetace did not show expansion of these genes. The strikingly different gene duplication and loss patterns in Onygenales may be associated with the different pathogenicity of these species. Interestingly, likelihood ratio tests (LRT) of both M35 family and M36 family genes suggested that several branches leading to the duplicated genes in dermatophytic and Coccidioides fungi had signatures of positive selection, indicating that the duplicated Mep genes have likely diverged functionally to play important roles during the evolution of pathogenicity of dermatophytic and Coccidioides fungi. The potentially positively selected residues discovered by our analysis may have contributed to the development of new physiological functions of the duplicated Mep genes in dermatophytic fungi and Coccidioides species. Our study adds to the current knowledge of the evolution of Meps in fungi and also establishes a theoretical foundation for future experimental investigations.